TY - JOUR
T1 - Emotional behavior in heterozygous rolling mouse Nagoya Cav2.1 channel mutant mice
AU - Takahashi, Eiki
AU - Niimi, Kimie
AU - Itakura, Chitoshi
N1 - Funding Information:
All animal procedures were approved by the Animal Experiments Committee of RIKEN, and all animals were cared for and treated humanely in accordance with institutional guidelines for animal experimentation. The RMN strain was found among descendants of a cross between the SIII and C57BL/6 strains and has been maintained by intercross mating ( Oda, 1973 ). The RMN strain was provided by the RIKEN BioResource Center, with support from the National BioResource Project of the Ministry of Education, Culture, Sports, Science, and Technology of Japan.
Funding Information:
This work was supported by the Program for Research and Development from RIKEN.
PY - 2011/3
Y1 - 2011/3
N2 - Although rolling mouse Nagoya, a Cav2.1α1 mutant, exhibits ataxia and elevated serotonin concentrations, heterozygous mice have not been examined in detail. Patients with heterozygous mutations in this orthologous gene exhibit neurological disorders. To examine the emotional behavior of heterozygous mice, we used behavioral tasks and examined Cav2.1α1 message levels, tryptophan hydroxylase expression patterns, and monoamine concentrations in 2- and 22-month-old mice. Reduced anxiety in the elevated plus maze, light-dark exploration, and marble-burying behavioral tests and reduced depression in the forced swimming and tail suspension tests were observed in 22-month-old heterozygous mice compared to aged-matched wild-type mice. The levels of mutant-type Cav2.1α1 message, phosphorylation of tryptophan hydroxylase, and serotonin increased in the brainstems of 22-month-old heterozygous mice. No difference was observed between 2-month-old heterozygous and wild-type mice in these analyses. These findings suggest that heterozygous mice show age-related emotional changes due to alterations in the serotonin system associated with mutant-type Cav2.1α1, and that heterozygous mice may represent a novel model to delineate the interaction between Cav2.1 function and synaptic transmission.
AB - Although rolling mouse Nagoya, a Cav2.1α1 mutant, exhibits ataxia and elevated serotonin concentrations, heterozygous mice have not been examined in detail. Patients with heterozygous mutations in this orthologous gene exhibit neurological disorders. To examine the emotional behavior of heterozygous mice, we used behavioral tasks and examined Cav2.1α1 message levels, tryptophan hydroxylase expression patterns, and monoamine concentrations in 2- and 22-month-old mice. Reduced anxiety in the elevated plus maze, light-dark exploration, and marble-burying behavioral tests and reduced depression in the forced swimming and tail suspension tests were observed in 22-month-old heterozygous mice compared to aged-matched wild-type mice. The levels of mutant-type Cav2.1α1 message, phosphorylation of tryptophan hydroxylase, and serotonin increased in the brainstems of 22-month-old heterozygous mice. No difference was observed between 2-month-old heterozygous and wild-type mice in these analyses. These findings suggest that heterozygous mice show age-related emotional changes due to alterations in the serotonin system associated with mutant-type Cav2.1α1, and that heterozygous mice may represent a novel model to delineate the interaction between Cav2.1 function and synaptic transmission.
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U2 - 10.1016/j.neurobiolaging.2009.03.001
DO - 10.1016/j.neurobiolaging.2009.03.001
M3 - Article
C2 - 19345443
AN - SCOPUS:79952900159
VL - 32
SP - 486
EP - 496
JO - Neurobiology of Aging
JF - Neurobiology of Aging
SN - 0197-4580
IS - 3
ER -